Firstly, although you use the worlds 'Living Cells' I am going to just talk about, lets say 'Functional Cells', because I don't think a living cell is anything other than a collection of molecules which happen to all play a role in a stable system which functions to propogate itself.

If you are wondering how it all came together in the first place, I am not going to start having stabs in the dark about it, because how it all started is most likely absolutely nothing like what we have now. What we have now in bacteria, are highly optimized cells which have been 'perfected' by billions of years of competition between the variations presented in the course of replication. I will instead talk about what makes a cell functional these days, as we understand it.

These days, there are pretty much 4 major molecules that I can think of. Lipids, Proteins, Ribose Nucleic Acids and Deoxyribose Nucleic Acids.

Lipids are amphipathic molecules (that is, they have one end Hydrophobic (water hating), and one end Hydrophilic(water loving) (For a demonstration of a Hydrophobic molecule, pour oil into a glass of water.) This property of lipids causes them to naturally form themselves into a membrane layer. The water hating half do whatever they can to get away from the water, so they all stick together, while the water loving half stick out into the watery suroundings. Because of the shape of Phospholipids and Glycolipids, this results in a lipid Bilayer. That is two lipid molecules, tail to tail, all lined up next to each other. and show you what i mean.

In the case of some other types of lipids, Miceles are formed, which are basically just a ball of lipids, rather than a bilayer... I think this is how cells store fat in our body...Otherwise they are not really vitally important to a functional cell. The Lipid Bilayer is though, it is the skin, the thing which keeps the cell together.

Of course though, it does not work alone, about 50% of the cell membrane (by mass) is made up of membrane associated proteins. (You can see some examples of these in the image above. I'll taolk about proteins in my next post.

I have changed my mind, I won't talk about proteins now, i will talk about DNA. Unlike Lipids, which self assemble themselves into Membranes as a matter of course, DNA, RNA and proteins do not. It is these molecules which really make up everything which is interesting about functional cells. Lipids are just a good place to start because they don't need anything to do what they do.

DNA is a molecule which consists of three basic parts. There is the Sugar backbone (Deoxyribose)(Ribose in the case of RNA), there is the Base (Purines: Adenine, Guanine. Pyrimidines: Cytosine, Thymine (And Uracil in the case of RNA)), and then there is the phosphate molecule which connects each sugar molecule to the next (making up the back bone)

One of the important features of a functional cell, is that it is able to copy itself. To do this it has to be able to make all of its components (proteins and RNA molecules), and copy its DNA. DNA encodes all of the RNA and protein molecules, while the base pairing nature of the double Helix allows DNA to be duplicated. See in the image above how the C binds to the G and the T binds to the A? Well in replication of DNA, all that happens is that these two strands are pulled apart and a protein/RNA complex reads one DNA strand and grabs loose Nucleotides (Base + Sugar + Triphosphate molecules) which match up to the strand which is being read and adds them to the new strand being created. Eventually, the both of the strands are copied, and you end up with two DNA molecules.

This is how DNA is copied, and this is possible the most important part of a functional cell.

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Summary so far: Membranes act as the skin, differentiating inside from outside, and they self assemble. DNA replicates itself by its chemical propensity to base pair with only one other base (this catalysed by protein and RNA molecules, but it is based on the natural chemical nature of DNA molecules (which RNA mirrors in the catalysis).

Two of the main Molecules present in cells, behaving like chemicals, creating 'life'.

Next in the process is RNA. RNA is very similar to DNA, its just got an extra oxygen, and one of its bases is Uracil instad of Thymine.

Anyway, its role in this process is that DNA is transcribed into RNA before anything else is done with the code that DNA holds. RNA bases match up to the DNA bases (once again, this is catalysed by a protein/RNA molecule) much like DNA replication and a long RNA chain is made (no where near as long as the whole DNA chain though).

These RNA chains can then either fold up into their own function structures and do stuff (such as the molecules which help replicate DNA, transcribe DNA, Translate RNA and other functions), or then can remain as linear molecules and be translated into proteins. (these are called Messenger RNA molecules)

tRNA's bind to the mRNA molecule, recognise three bases (called a Codon) and attaches an Amino Acid (the molecules which make up proteins) which is associated with those three bases. This process proceeds until it reaches a stop codon, and the protein is made (almost).

The Genetic Code (which dictates which Amino Acid each Codon represents) can be seen here:

edit: Tried to figure out how to make the images appear in the text. Have we lost this feature in the move from PF2?

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Summary: Lipids create the barrier, DNA replicates itself because of base pairing interactions, RNA is encoded because of the same Base Pairing interactions, and RNA is then used to encode proteins.

The mRNA is translated by tRNA base pair matches to the Codons, and the Amino Acids that attach to each tRNA molecule are added to the growing chain of Amino Acids that make the Protein (See here: ). I perhaps should have also pointed out in the RNA post, that there a many tRNA's (64 is it? One for each codon? Or its at least something near that) and each tRNA binds to its own specific Amino Acid, and has its own specific Codon recognition sequence (Anticodon).

Anyway, point being, that through the base pair recognition system, RNA is made, and RNA uses this to create proteins. Proteins are then quite unlike anything else. Made up from 20 different Amino Acids stuck together according to the sequence encoded in the DNA, each amino acid has its own distinct properties. In general though, they are each classified according to their side chain charge and polarity.

These two factors create degrees of Hydrophobicity and electrostatic attraction-repulsion between parts of the protein and between the protein and other molecules.

Attractions etc within the Protein: See, the order of the Amino Acids in a protein is what is known as the primary structure. After that, the secondary structure is how that chain folds into 'Beta Sheets' and 'Alpha Helices'. The {b]Tertiary Structure[/b] is how those alpha helices, beta sheets and loops all come around to folding into a globule molecule (a process which is based on the hydrophilic Amino Acids trying to get on the inside, and the Bydrophobic molecules trying to get to the outside more than anything else, same as Lipids huh?). The Tertiary Structure is then how these globular proteins interact with one another to make even larger multiple part molecules. (This image is an example of how protein tertiary structures are drawn, where the straight ribons represent beta sheets and the helical ribbons are alpha helices. )

And that, is Proteins.

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How does this make a functional cell? Well, proteins are really the workhorse. Everything that a cell does is pretty much reliant on proteins. Proteins catlayse reactions (breaking down molecules to make energy, utilising energy carrying molecules to construce functional molecules etc), they form large structural molecules like Collagen and Elastin, they form motors like the ATP Hydrolase molecule, Cilia and Flagellum. Proteins are all through the membrane making the membrane into something infinitely more impressive than 'Just a barrier'. The membrane is now the basis for nearly everything the cell does (Oxygen use occurs in the 'Electron Transport Chain' which is all membrane related. It is by using membranes to create an electron gradient (ie make one side of the membrane more charged than the other, and allow those electrons to flow through an Protein channel which utilises this Electron flow to synthesis energy carrier molecules. Essentially same idea as Hydroelectricity.) all because of the proteins that exist in the membrane.

So to sum up: Membrane self assemble. DNA has chemical properties which dictate how it should be replicated and transcribed. RNA has chemical properties which dictate how it is transcribed from DNA, and how it then folds up, which has practical applications in then translating mRNA molecules into Proteins. Proteins are therefore coded from the mRNA molecule into particular primary sequences, which, because of particular chemical reactions, consequentially fold in secondary, tertiary and quaternary structures. Based on these 4 structural elements, proteins have a range of functions which create the amazing functionality of the cell.

There is no single 'Element' which seperates a 'living cell' from molecules. A living cell, is just a complex collection of molecules doing the stuff they would be doing outside of a cell given the right components/environment. The cell just happens to provide all of those elements.

So, after all you said, how do you explain that synthesizing a living cell has never been achieved? After all, with self-assembling membranes and DNA replicating through RNA, it should be standard procedure.... but in spite of all this knowledge, the synthesis does not work. This knowledge seems to have a serious gap.

Instead of talking about 'living' cells you prefer to call them 'functional cells', assuming that by replicating cells are performing all of what cells can do. But then that leaves out the essential element of what makes an organism into an organism -- as opposed to a mere heap of tumorous luxuration.

Leaving out "how it all came together in the first place" is not a good basis, because then the rest of the talk is like building the first floor of a house on a floating foundation.

Indeed, the Miller type experiments never get beyond some basic elements, and that's where the process stops. And already very large polymerization is a limit insofar as it must be highly organized for a real cell membrane to get assembled, not only some tissue of that sort.

You give a little clue in saying "given the right components / environment" but then close down again in saying "The cell just happens to provide all of those elements". From what you say, making it sound so easy, the synthesis of living cells should pose no problems. And yet in practice it does, even enormous ones.

Originally posted by sascha So, after all you said, how do you explain that synthesizing a living cell has never been achieved?

Simple: Cells are not simple. They are a complex network of intricatly interacting components far beyond our understanding of them. But all of that complexity comes almost entirely from those four molecules. The DNA and RNA part is relatively simple, the lIpid part is easy...its the proteins that are a pain in the bum to figure out. They are complex, varied, and can do almost anything.

After all, with self-assembling membranes and DNA replicating through RNA, it should be standard procedure....
Leaving out "how it all came together in the first place" is not a good basis, because then the rest of the talk is like building the first floor of a house on a floating foundation.

See, these two points are related. I left out the 'How it all came together' because we don't know, and yet the 'How it all came together' holds the key to why we cant synthesis cells in vitro. It is unreasonable to believe that a cell as complex as the types we see today are anything like what they were like when this game of life started, so trying to synthesis an 'end product' cell using natural processes is ludicrous. We would need a test tube the size of the earth, and 3 billion years. Not a small flask and 3 years in a lab.

Instead of talking about 'living' cells you prefer to call them 'functional cells', assuming that by replicating cells are performing all of what cells can do. But then that leaves out the essential element of what makes an organism into an organism -- as opposed to a mere heap of tumorous luxuration.

What is that essential element?

I left it out because I have no idea what else a cell does other than keep itself alive (maintaining itself in a state viable to replicate) long enough to leave as many offspring as it can, thus perpetuating the functional procedure that was bred into it via evolution. If cells do anything more than that, please tell me.

You give a little clue in saying "given the right components / environment" but then close down again in saying "The cell just happens to provide all of those elements". From what you say, making it sound so easy, the synthesis of living cells should pose no problems. And yet in practice it does, even enormous ones.

Oh, my words have nothing to do with the synthesis of living cells, my words only relate to the amazing specificity that cells no posses in their functionality.

The right environment/components thing is shown by processes such as PCR. By simply mixing the Nucleotides (A, C, T and G), a DNA template, two primers (one for each direction) and Taq POlymerase, the Template is replicated exponentially. This process of DNA replication does not require some special 'Life force' or anything like that to occur, it just occurs. BUT, if there was no DNA, no Nucleotides, no Polymerase or no primers, then it wouldn't occur. Cells ensure that all of those parts are present inside it, because if they weren't, the cell would not be able to replicate, and then it would never make it this far... The only reason we see what we do, is because it happened (somehow), and it works. If it didn't work, we wouldn't see it. (and don't)

Now, as for the synthesis of lIving cells, I think this misses the point on many levels, and hopefully now you will see why I think this. Based on the fact that early 'life' would not have been cells like we now know them, something like PCR is most likely the first form of life.

It is unlikely, but possible that the first 'life form' (or, to say something less controversial, the first replicating molecule was an RNA molecule of a sequence that folded up into an RNA Polymerase type molecule. The molecule could then be duplicated by simple complementary nucleotide addition, and then when there were many copies of itself, it could even catalyse this process. And say this RNA molecule was at the bottom of the ocean, near a Hydrothermal vent, and the vent pushed it up where it was cooler and could flow down to the ground again away from the vent, but as it approaches the ground, the current would pull it back into the vent again, sucking it in, then blowing it up. In this way you get a hot/cold cycling process, much like PCR.

This is all entirely fictionally made up from the top of my head, but this is a reasonably valid hypothesis for something along the lines of how replicating molecules may have started. And from there, you ahve replication, heredity, and differential fitness: You have evolution. Things will onyl get more and more impressive.

Sure cells are complex -- and there seems to be Complexity Theory as the saviour, for modelling all that interaction. But in the end the modelling is merely a description of the pattern, not more than that. Your word "almost" before "entirely" is rather important.

Concerning the 'How it all came together', I agree that one can invent scenarios like the PCR process you present. But then, what is gained by that in terms of really understanding the relevant bit of an organism being an organism, not just replicating stuff? If there is no method for finding the appropriate access to that, there is a need to ask what kind of knowledge this is, and whether other approaches might be more fruitful.

This leads to your question "What is that essential element?". My point is that one has to ask this very question very open-mindedly, not shoving it away by finding quick escapes. ((I have an viewpoint in this: the categories, through which science is currentliy thinking, do not allow it to find that essential element. This is not the problem of nature, but of science -- i.e. of the chosen categoreality in the usual approaches. What I say has nothing to do with vitalism or anything like that, which remains within the good old self-limited categoreality.))

I am curious what you will be able to draw from the mentioned literature.

Originally posted by sascha
Sure cells are complex -- and there seems to be Complexity Theory as the saviour, for modelling all that interaction. But in the end the modelling is merely a description of the pattern, not more than that. Your word "almost" before "entirely" is rather important.

Concerning the 'How it all came together', I agree that one can invent scenarios like the PCR process you present. But then, what is gained by that in terms of really understanding the relevant bit of an organism being an organism, not just replicating stuff?

This is the same problem Iacchus had before, and the problem is that one continues to try and place an anthropocentric view on the "nitty-gritty" of Science. IOW, the true hard sciences have no room for making humans "special", and any attempts to do so are philosophically valid but no scientifically.

The difference between understanding what makes an organism an organism and remaining at the view of heaps of blindly replicating stuff has nothing whatsoever to do with any anthropocentric view on whatever. How do you reach this conclusion?

In fact, things are just the other way around: the 'scientific' approach makes its 'God's view' from outside the object into the only acceptable stance. This is anthropocentrism in its purest form. The fact that this fact is denied and rejected is part of the anthropocentric gesture.

Originally posted by Another God
It is unlikely, but possible that the first 'life form' (or, to say something less controversial, the first replicating molecule was an RNA molecule of a sequence that folded up into an RNA Polymerase type molecule.

The guy is saying that translation evolve first then came transcription.

Originally posted by Another God
The molecule could then be duplicated by simple complementary nucleotide addition, and then when there were many copies of itself, it could even catalyse this process. And say this RNA molecule was at the bottom of the ocean, near a Hydrothermal vent, and the vent pushed it up where it was cooler and could flow down to the ground again away from the vent, but as it approaches the ground, the current would pull it back into the vent again, sucking it in, then blowing it up. In this way you get a hot/cold cycling process, much like PCR.

AG, I don't think it like to have happen. Taq polymerase for PCR is used at high temperature because it evolve to be high temperature resistant. It it more likely that DNA evolve as a single strand and that polymerase worked at the ocean temperature (4 to 25 C). Then as the cellular organisation became more complex, DNA became double stranted and as cell went out their original niche polymerase became more stable at higher temperature (more than 25C).

You explanation to how it is related is good but you guys should read the article I point out earlier because the explanation about connection of the elements and evolution make a lot of sense.

That last bit Ian was the bit which I meant was unlikely. I didn't actually think it happened like that, but instead was trying to imply that the original 'life' would have been quite unlike cellular that we now have. It would ahve simply been the replicating core. Since I have no idea how this can happen without all of the complex cellular machinery we now have, I tried to sketch a dodgy possibility to show how something like it might happen without needing to intracellular environment...

I'll get back and reply to everything else tomorrow...I have 2 essays to write today.